USPTO Patents Application 09557823

APPROVr.O
BY

ORAFTSHAH

O.G, FfQ.

CLASS

SUBCLASS

2/22

10 20 30 40 50 60

mm i f ATGCCTATGTTCATaTGMCAGCMTGnCCCCGCGCCTCOJTGCCAGAGGGGIITCTG

>hm i f ATGCCGATGTTCATCGTAMCACCM^

10 20 30 40 50 60

70 80 90 100 110 120

mm if TCGGAGCTCACCCAGCAGCTGGCGCAGGCCACCGGCAAGCCCGGACAGTACATCGCAGTG

>hm i f TCCGAGCTCACCCAGCAGCTGGCGCAGG^^

70 80 90 100 110 120

130 140 150 160 170 180

mm i f CACGTGGiCCCGGACCAGCTCATGACTTTTAGCGGCACGAACGATCCCTGCGCCCTCTGC

>hm i f CACGTGGTCCCGGACCAGCTCATGGCCTT

130 140 150 160 170 180

190 200 210 220 230 240

mm i f AGCCTGCACAGCATCGGCAAGATCGGTGGTGCCCAGAACCGCAACTACAGIAAGCTGCTG

>hm i f AGCCTGCACAGCATCGGGMGATCGGCGGCG^^

190 200 210 220 230 240

250 260 270 280 290 300

mm i f TGTGGCCTGCtGTCCGATCGCCTGCACATCAGCCCGGACCGGGICTACATCAAGT ATTAG

>hm i f TGCGGCCTGCTGGCCGAGCGCCTGCGCATCAGGC^^^

250 260 270 280 290 300

310 320 330 340

mmi f GACATGAACGCTGCCAACGTGGGCTGGAACGGIICCACCTTGGCTTGA

>hm i f GACATGAACGCGGCGAGTGTGGGCTGGAACAACTCCACCTTCGCCT
310 320 330 340

FIG.2

1

APPROVED
BY

O.G . FIG.

CLASS SUBCLASS

3/22

start
I

CCATGCCTATGTTCATCGTGAACACCAATGTTCCCGGCGCC

TCCGTGCCAGAGGGGTTTCTGTCGGAGCTCACCCAGCAGCTGGCGCAGGCCACCGGCAAG

CCCGCACAGTACATCGCAGTGCACGTGGTCCCGGACCAGCTCATGACTTTTAGCGGCACG

AACGATCCCTGCGCCCTCTGCAGCCTGCACAGCATCGGCAAGATCGGTGGTGCCCAGAAC

CGCAACTACAGTAAGCTGCTGTGTGGCCTGCTGTCCGATCGCCTGCACATCAGCCCGGAC

CGCTCCTACAGCAAGCTGCTGTGCGGCCTGCTGGCCGAGCGCCTGeGCATCAGCCCGGAC

CGGGTCTACATCAACTATTACGACATGAACGCTGCCAACGTGGGCTGGAACGGTTCCACC

AGGGTCTACATCAACTATTACGACATGAACGCGGCCAGTGTGGGCTGGAACAACTCCACC

TTCGCTTGAGTCCTGGCCCCACTTACCTGCACCGCTGTTC
t

stop

FIG.3

BY

DRAFfSHAK

O.G. FIG.

CLASS

SUBCLASS

4/22

o

Csl

GO

o
I

UJ
CO

cn
o

o

Q-

§ s

Q-

CO

<:
or

i

CO
U-

Q-

O
OO

-< •

• <c

Li_ •

• U-

1 — •

• COI

co| •

NM

o •

• o

AN

AN

^ :

:|

z •

• Q

>- •

• >-

>- ;

•

i i

• >

Q •

Q- •

• Q-

CO •

• tn

' or

a:: -

• or

- LxJ

CO

:8

8 :

• 1

• ii^:

COI •

• CO

•

• >-

- CO

or •

• or

i i

• O

• <c

o ■

• o

O ;

; O

'

O ;

; O

CO •

• CO

in ■

• zn

1 ■

CO ■

• CO

u

u. r iQ.

BY

GL

ASS

SUBCLASS

U(\Ar J on AN j

1 , , g

5/22

100

-4 -3-2-1 0 1

Log MIF (ng/ml)

FIG. 5

I3y

GLAS

SUBCLASS

6/22

100

5

CO

80
60
40
20
0

P=0.003

^H-

1

LPS

LPS + MIF

I —

20 40

Hours after challenge

FI6.6A

60

100
^ 80

w 60

>

I 40 +
(/)

20 +
0

1

P<0.0001

+

24

Anti-MIF

NRS

Saline

48

72

96

120

Hours after LPS challenge

FIG. SB

APPRom. j o.G. FIG.

8v j cuss

gaAFTSHAHl

SUeCLASS

7/22

g

CO

100

80 --

60 -

40 -

20 ■

12

24

36

48

60

72

HOURS POST-CHALLENGE

FIG.7

APPROVEO

BY

[O.G. FIG.

SU3GLASS

8/22

LPS ng/ml

o

Ul
Ul

m

yi

=

4=

nj

Ul
Q

m

r — — - — 1

C 0 0.1 1 10 100 Mr MIF (K)

~ L -29.0

., ■ '•••.1

■ # - 18.4

- 6.2

FIG. 8

APPROVKO
BY

'O.G. FIG.

GLASS

SUBCLASS

9/22

70/22

APPf^ov£o[O.G. FIG.

BY

CLASS SUBCLASS

12/22

By

ORAfrSHAH

O.CFIG.

CLASS

SUBCLASS

13/22

3SV3aoNi- aioj 'Jiw

Or

'O.G.fiG.

CLASS jsiiSGLASi

14/22

Ul

aseajoui-p|o^ 'dlllAI

jO.G.FIG.

{ CLASS (subclass

15/22

1 APPRQy^fi

u.u, FIG.

j DY

CLASS

SUBCLASS

j UffAf- 1 SHAN

16/22

LPS (ng/ml)

rMIF 01 0-3 10-2 iq-I 1 10 102

FIG.16A

LPS (ng/ml)

rMIF 0 tO-3 10-2 lO'^ 1 10 102

FIG.16B

IFNy (100 U/ml) + LPS (ng/ml)
rMIF ^ 10-3 10-2 lO"** T 10 102

FIG. 16C

BY

O.G-FIG.

CLASS

SUBCLAiiS

17/22

LPS (ng/ml)

FIG. 17

i

APPRovfc-D jo.G. F{G. ■

1 CLASS

SUQGLASS

18/22

19/22

TNFg IL-lfi IFNy IL-6
(K) rMIF ^lo 1 ' 10 1 'l03 102 ' 10 1 '

18.4 —
14.3 —

6.2 —
2.9 —

FIG. 19

. 1 CLASS

sObcla'ss

20/22

■4%

E

u.
z

1400
1200
1000
800
600
400
200
0

10 100
rMIF (ng/ml)

1000

FIG. 20

APPROVEO
BY

0KAFT5HAM

'O.G. FIG.

CLASS

SUBCLASS

DEXAMETHASONE (n )

-14 -12 -10 -8 -6
10 10 10 10 10 C MIF

21/22

RAW

FIG. 21A

4-PRE6NENE(ld'^M)
+ DEXAMETHASONE (n)

10-1^10-12 ,Q-10^Q-8 ^

MIF

Urn

RAW

FIG. 21B

1 u.u. r |b.

1 CLASS
^DRAf rSHAN f

SUBCLASS

22/22

2.9 —

FIG. 22